Acute Myeloid LeukemiaPhase 1NCT03483948
Phase I Study of HMPL-523+Azacitidine in Elderly Patients With Acute Myeloid Leukemia
A Phase 1 study testing HMPL-523 and Azacitidine in people with Acute Myeloid Leukemia, run by Hutchison Medipharma Limited at 1 site in China.
Trial summary
This is a Phase I, open-label, non-randomized, multicenter study to evaluate the safety, pharmacokinetics and preliminary efficacy of HMPL-523 in combination with Azacitidine in previously untreated elderly patients with AML who are not eligible for standard induction therapy. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- HMPL-523 and Azacitidine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteChina
- Study dates
- 9 Oct 2018to 9 Sep 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Subject must have confirmation of AML by WHO criteria, except for APL (M3)
- Subject must be ≥ 65 years of old and be ineligible for treatment with a standard cytarabine and anthracycline induction regimen due to co-morbidity or other factors
- Subject must have received no prior treatment for AML with the exception of hydroxyurea
- ECOG performance status of 0-1. For dose-expansion stage, ECOG PS of 2 will also be eligible
Who cannot join
- Subject has received treatment of hypomethylating agent and/or chemo therapeutic agent for MDS or MPN
- Subject has known active CNS involvement or extramedullary sarcoma from AML
- Subject has favorable risk cytogenetics as categorized by the NCCN Guidelines Version 1, 2018 for Acute Myeloid Leukemia, such as inv(16) or t(16;16) or t(8;21) or t(15;17)
- Subject has a white blood cell count > 25 × 109/L (Hydroxyurea is permitted to meet this criterion)
- Subject with serum amylase or lipase > the ULN
- Subject is known to be positive for hepatitis B or C infection with the exception of those with an undetectable viral load.
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- Subject who don't have enough liver or renal function
- Subject with New York Heart Association (NYHA) Class III or greater congestive heart failure
- Subject received herbal therapy ≤ 1 week prior to initiation of study treatment
- Subject received prior treatment with any SYK inhibitors (Fostamatinib) or FLT3 inhibitor (Quizartinib) or multi-target inhibitor with SYK or FLT3 inhibition activity (Midostaurin)
Trial locations and contacts
1 site in 1 country.
China1 site
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences
Tianjin, Tianjin Municipality, 300020
About this study
Official title: A Phase I Study of Safety, Pharmacokinetics and Efficacy of HMPL-523 With Azacitidine in Elderly Patients With Previously Untreated Acute Myeloid Leukemia
This is a Phase I, open-label, non-randomized, multicenter study to evaluate the safety, pharmacokinetics and preliminary efficacy of HMPL-523 in combination with Azacitidine in previously untreated elderly patients with AML who are not eligible for standard induction therapy.
Read the detailed description
There are two stages in this study: a dose-escalation stage (stage 1) and a dose-expansion stage (stage 2).
Dose-escalation stage (stage 1):
The conventional 3+3 design (3 patients per dose cohort, with the potential to add additional 3 patients to the same cohort to further evaluate toxicity) will be applied for dose escalation and maximum tolerated dosage determination. Approximately 12 to 18 dose limited toxicities evaluable patients will be enrolled. A dose of HMPL-523 up to 800mg will be taken orally once daily continuously through a 28-day Cycle of study treatment. Azacitidine will be administered subcutaneously, beginning on Day 1 through Day 7 of each Cycle.
Dose-expansion stage (stage 2):
This phase is to further evaluate the safety, pharmacokinetics and preliminary efficacy of HMPL-523 in combination with Azacitidine in approximately 28 previously untreated elderly patients with AML. Patients will receive HMPL-523 in combination with Azacitidine in a 28-day cycle continuously until disease progression/relapse, death, or intolerable toxicity, whichever comes first.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- HMPL-523, Azacitidine
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HMPL-523Drug
HMPL-523 tablet
AzacitidineDrug
Also called Vidaza
Azacitidine Injection
| Study group | Role | What they receive |
|---|---|---|
| HMPL-523 & Azacitidine | Experimental | HMPL-523 will be taken orally once daily continuously through a 28-days Cycle of study treatment. Azacitidine will be administered subcutaneously, beginning on Day 1 through Day 7 of each Cycle. Receives: Drug: HMPL-523; Drug: Azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Event (AE) monitoring of HMPL-523 in combination with azacitidine
AE monitoring will be assessed by evaluation of study drug exposure, AEs , serious AEs, all deaths, as well as laboratory determinations and vital sign parameters.
Measured: Measured from the first dose to within 30 days after the last dose.
Overall response rate (ORR)
Overall response rate will be defined as the proportion of subjects who achieve a complete remission (CR), complete remission incomplete (CRi), Morphologic leukemia-free state (MLFS), or partial remission(PR) per 2017 European Leukemia Net (ELN) recommendations
Measured: Measured up to 1 year after the last subject has enrolled or all the subjects have finished their last EFS follow up, whichever comes first.
Secondary outcomes (13)
Maximum plasma concentration (Cmax) of HMPL-523
Maximum concentration, occurring at Tmax.
Measured: Measured on the cycle 1 day 7, cycle 1 day 8, cycle 1 day 28 and cycle 2 day 1.
The time to Cmax (peak time, Tmax) of HMPL-523
The time at which maximum plasma concentration (Cmax) is observed.
Measured: Measured on the cycle 1 day 7, cycle 1 day 8, cycle 1 day 28 and cycle 2 day 1.
The area under the plasma concentration-time curve (AUC) from 0 to the time of the last measurable concentration (AUCt) of HMPL-523
The area under the plasma concentration-time curve (AUC) from 0 to the time of the last measurable concentration.
Measured: Measured on the cycle 1 day 7, cycle 1 day 8, cycle 1 day 28 and cycle 2 day 1.
Half-life (t1/2) of HMPL-523
The time required for the concentration of the drug to reach half of its original value.
Measured: Measured on the cycle 1 day 7, cycle 1 day 8, cycle 1 day 28 and cycle 2 day 1.
Clearance (CL) of Azacitidine
Clearance is defined as the rate at which drug is cleared from the blood.
Measured: Measured on the cycle 1 day 7 and Cycle 1 day 8.
The area under the plasma concentration-time curve (AUC) from 0 to the time of the last measurable concentration (AUCt) of Azacitidine
The area under the plasma concentration-time curve (AUC) from 0 to the time of the last measurable concentration.
Measured: Measured on the cycle 1 day 7 and Cycle 1 day 8.
Half-life (t1/2) of Azacitidine
The time required for the concentration of the drug to reach half of its original value.
Measured: Measured on the cycle 1 day 7 and Cycle 1 day 8.
Steady-state concentration(Css) of Azacitidine
The average concentration of drug at steady state
Measured: Measured on the cycle 1 day 7 and Cycle 1 day 8.
Complete Remission Rate of Minimal Residual Disease (MRD) Negativity （CR MRD- rate）
CR MRD- rate will be defined as the proportion of subjects who achieve a CR and has a negative RT-qPCR or MFC at the same time.
Measured: Measured up to 1 year after the last subject has enrolled or all the subjects have finished their last EFS follow up, whichever comes first.
Event Free Survival (EFS)
EFS will be defined as the number of days from the date of first dose to the date of earliest recurrence or PD or death.
Measured: Measured up to 1 year after the last subject has enrolled or all the subjects have finished their last EFS follow up, whichever comes first.
Disease-free Survival (DFS)
DFS will be defined as the number of days from the date of composite complete response (CR + CRi) to the date of earliest recurrence or death.
Measured: Measured up to 1 year after the last subject has enrolled or all the subjects have finished their last EFS follow up, whichever comes first.
Overall Survival (OS)
OS will be defined as the number of days from the date of enrollment to the date of death.
Measured: Measured up to 1 year after the last subject has enrolled or all the subjects have finished their last EFS follow up, whichever comes first.
Cumulative incidence of relapse (CIR)
CIR will be defined as the cumulative proportion of subjects who has relapsed after achieving a composite complete response (CR + CRi).
Measured: Measured up to 1 year after the last subject has enrolled or all the subjects have finished their last EFS follow up, whichever comes first.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2018
- Study start9 Oct 2018
- Primary completion9 Sep 2019
- Study completion9 Sep 2019
Why it stopped: Slow Enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hutchison Medipharma Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jianxiang Wang, Prof., Principal investigator, Chinese Academy of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03483948
- Sponsor's protocol ID
- 2017-523-00CH3
- Status last verified
- Nov 2019
- First submitted
- 23 Mar 2018
- Last updated
- 20 Nov 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Safety, Pharmacokinetics and Efficacy of HMPL-523 With Azacitidine in Elderly Patients With Previously Untreated Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT03483948
- Acronym / sponsor ID
- 2017-523-00CH3
- Conditions
- Acute Myeloid Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow Enrollment
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Hutchison Medipharma LimitedIndustry (pharma, biotech, devices)
- Study start
- 9 Oct 2018 (actual)
- Primary completion
- 9 Sep 2019 (actual)
- Study completion
- 9 Sep 2019 (actual)
- First posted
- 30 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase I, open-label, non-randomized, multicenter study to evaluate the safety, pharmacokinetics and preliminary efficacy of HMPL-523 in combination with Azacitidine in previously untreated elderly patients with AML who are not eligible for standard induction therapy.
Detailed description
There are two stages in this study: a dose-escalation stage (stage 1) and a dose-expansion stage (stage 2).
Dose-escalation stage (stage 1):
The conventional 3+3 design (3 patients per dose cohort, with the potential to add additional 3 patients to the same cohort to further evaluate toxicity) will be applied for dose escalation and maximum tolerated dosage determination. Approximately 12 to 18 dose limited toxicities evaluable patients will be enrolled. A dose of HMPL-523 up to 800mg will be taken orally once daily continuously through a 28-day Cycle of study treatment. Azacitidine will be administered subcutaneously, beginning on Day 1 through Day 7 of each Cycle.
Dose-expansion stage (stage 2):
This phase is to further evaluate the safety, pharmacokinetics and preliminary efficacy of HMPL-523 in combination with Azacitidine in approximately 28 previously untreated elderly patients with AML. Patients will receive HMPL-523 in combination with Azacitidine in a 28-day cycle continuously until disease progression/relapse, death, or intolerable toxicity, whichever comes first.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HMPL-523 & Azacitidine | Experimental | Drug: HMPL-523, Drug: AzacitidineHMPL-523 will be taken orally once daily continuously through a 28-days Cycle of study treatment. Azacitidine will be administered subcutaneously, beginning on Day 1 through Day 7 of each Cycle. |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (4 listed)
- Subject must have confirmation of AML by WHO criteria, except for APL (M3)
- Subject must be ≥ 65 years of old and be ineligible for treatment with a standard cytarabine and anthracycline induction regimen due to co-morbidity or other factors
- Subject must have received no prior treatment for AML with the exception of hydroxyurea
- ECOG performance status of 0-1. For dose-expansion stage, ECOG PS of 2 will also be eligible
Key exclusion criteria (10 listed)
- Subject has received treatment of hypomethylating agent and/or chemo therapeutic agent for MDS or MPN
- Subject has known active CNS involvement or extramedullary sarcoma from AML
- Subject has favorable risk cytogenetics as categorized by the NCCN Guidelines Version 1, 2018 for Acute Myeloid Leukemia, such as inv(16) or t(16;16) or t(8;21) or t(15;17)
- Subject has a white blood cell count > 25 × 109/L (Hydroxyurea is permitted to meet this criterion)
- Subject with serum amylase or lipase > the ULN
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HMPL-523HMPL-523 tablet | Drug | HMPL-523 & Azacitidine |
| AzacitidineAlso: VidazaAzacitidine Injection | Drug | HMPL-523 & Azacitidine |
Primary outcome
Adverse Event (AE) monitoring of HMPL-523 in combination with azacitidine
Time frame: Measured from the first dose to within 30 days after the last dose.
AE monitoring will be assessed by evaluation of study drug exposure, AEs , serious AEs, all deaths, as well as laboratory determinations and vital sign parameters.
Overall response rate (ORR)
Time frame: Measured up to 1 year after the last subject has enrolled or all the subjects have finished their last EFS follow up, whichever comes first.
Overall response rate will be defined as the proportion of subjects who achieve a complete remission (CR), complete remission incomplete (CRi), Morphologic leukemia-free state (MLFS), or partial remission(PR) per 2017 European Leukemia Net (ELN) recommendations
13 secondary outcomes
Maximum plasma concentration (Cmax) of HMPL-523
Time frame: Measured on the cycle 1 day 7, cycle 1 day 8, cycle 1 day 28 and cycle 2 day 1.
The time to Cmax (peak time, Tmax) of HMPL-523
Time frame: Measured on the cycle 1 day 7, cycle 1 day 8, cycle 1 day 28 and cycle 2 day 1.
The area under the plasma concentration-time curve (AUC) from 0 to the time of the last measurable concentration (AUCt) of HMPL-523
Time frame: Measured on the cycle 1 day 7, cycle 1 day 8, cycle 1 day 28 and cycle 2 day 1.
Half-life (t1/2) of HMPL-523
Time frame: Measured on the cycle 1 day 7, cycle 1 day 8, cycle 1 day 28 and cycle 2 day 1.
Clearance (CL) of Azacitidine
Time frame: Measured on the cycle 1 day 7 and Cycle 1 day 8.
The area under the plasma concentration-time curve (AUC) from 0 to the time of the last measurable concentration (AUCt) of Azacitidine
Time frame: Measured on the cycle 1 day 7 and Cycle 1 day 8.
Half-life (t1/2) of Azacitidine
Time frame: Measured on the cycle 1 day 7 and Cycle 1 day 8.
Steady-state concentration(Css) of Azacitidine
Time frame: Measured on the cycle 1 day 7 and Cycle 1 day 8.
Complete Remission Rate of Minimal Residual Disease (MRD) Negativity （CR MRD- rate）
Time frame: Measured up to 1 year after the last subject has enrolled or all the subjects have finished their last EFS follow up, whichever comes first.
Event Free Survival (EFS)
Time frame: Measured up to 1 year after the last subject has enrolled or all the subjects have finished their last EFS follow up, whichever comes first.
Disease-free Survival (DFS)
Time frame: Measured up to 1 year after the last subject has enrolled or all the subjects have finished their last EFS follow up, whichever comes first.
Overall Survival (OS)
Time frame: Measured up to 1 year after the last subject has enrolled or all the subjects have finished their last EFS follow up, whichever comes first.
Cumulative incidence of relapse (CIR)
Time frame: Measured up to 1 year after the last subject has enrolled or all the subjects have finished their last EFS follow up, whichever comes first.
Results and safety
The study was stopped early (reason given: Slow Enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jianxiang Wang, Prof. principal investigator
Chinese Academy of Medical Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing HMPL-523 and Azacitidine in people with Acute Myeloid Leukemia, run by Hutchison Medipharma Limited at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Slow Enrollment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse Event (AE) monitoring of HMPL-523 in combination with azacitidine (time frame: Measured from the first dose to within 30 days after the last dose.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2019.